Blood adenosine levels as a novel diagnostic of seizures in humans

Epilepsy is the most common life-long brain disease and its diagnosis remains challenging needing the application of multiple criteria including patient history, seizure type and electroencephalography (EEG) recordings. The most reliable method is long periods under video surveillance during continuous EEG monitoring which is costly and only a limited amount of specialised hospital beds are available. Consequently, the majority of patients thought to have epilepsy are treated on the basis of observed behavioural changes during seizures leading to possible misdiagnosis. Thus, there is an urgent need to develop disease predictors (biomarkers) to accurately diagnose epilepsy. These biomarkers have to be easily accessible, easily measurable and preferably play a causative role during disease progression. The molecule adenosine increases in the brain after seizures and adenosine augmenting treatments have been proposed as novel therapy options in epilepsy. Adenosine is present at very low levels in the blood; however, no data on seizure-induced increases of adenosine in the blood have been reported to date. Most measurements to quantify adenosine concentrations in blood were depending on techniques poorly-suited to biomarker work. Recently developed adenosine biosensors enable us now to detect changes in blood adenosine levels rapidly and reliably. These biosensors are suitable for point of care testing as they are easy to handle, require minimal equipment and a minimum blood volume. Pilot data by the applicant now shows a dramatic increase in blood levels of adenosine after seizures in different animal models and patients. The project will undertake studies to establish the relationship between blood adenosine levels and seizure type and severity, timing of sampling and pathologic outcome. Together, these studies will establish blood adenosine measurement as a novel, sensitive and specific marker of seizure activity which can be used for seizure diagnosis and for prognosis of disease progression in patients.